Support for the hypothesis that rare coding variation also profoundly affects risk of certain “complex” diseases is growing and there are now a number of such examples including rare missense variants in CHEK2, ATM, NBS1, RAD50, BRIP1, and PALB2 in breast cancer [2], rare coding mutations in RAD51D and BRIP1 in ovarian cancer [3], [4], as well as rare coding variants in genes implicated in hyperglyceridemina [5] and colorectal cancer adenomas [6]. This evidence concerns the gene PALB2 and breast carcinoma.